This proposal plans to utilize a new mathematical method for optimal adaptive (feedback) control of pharmacokinetic models, coupled with methods for optimal monitoring of such models, to develop useful conversational clinical computer systems for achieving optimal adaptive control of drug therapy with lidocaine, theophylline, digitalis glycosides, and aminoglycoside antibiotics. This new optimal method has shown to be computationally as fast as current suboptimal feedback computer approaches to adaptive control previously employed. In addition, improved, more informative pharmacokinetic models will be employed in these proposed systems. Clinical evaluations of these new computer systems are proposed to compare, 1) precicion of achievement of the chosen therapeutic goals and 2) safety and efficacy. The proposed methods, coupled with the results of the proposed clinical evaluations, should lead to more informed (and carefully documented) minimum-cost (optimal) strategies to achieve any desired degree of accuracy in such adaptive control of therapy. Lastly, this proposal also seeks to develop automated systems for control of infusions with several of these drugs, to implement the optimal strategies for adaptive control at the bedside, giving entire infusion protocols (which are difficult to do manually) safely and reliably for an entire intensive care unit or coronary care unit.